1. Field of the Invention
The field of the invention pertains generally to medicine, pathology and oncology. More particularly, it addresses the treatment of breast cancer, such as triple-negative breast cancer, using a transmembrane prostate androgen induced (TMEPAI)-directed therapy.
2. Related Art
Although triple-negative breast cancers (TNBC) represent a relatively small percentage (15-25%) of total breast cancer cases, it is responsible for a disproportionately higher number of breast cancer deaths with shorter recurrence times and fewer therapeutic options in young women and minorities. TNBCs are negative for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) and are characterized by frequent ductal involvement, high grade, and high growth rates. Despite advances in treatment of ER-positive and HER2-positive breast cancers, there has been less progress in the treatment of ER-negative TNBC due to lack of focused targets that critically determine their growth, invasion and metastasis.
So far in the literature and patents the focus has been to inhibit TGF-β/Smad signaling as a therapeutic approach (see Bonafoux & Lee, 2009). In contrast, the inventors' prior studies exploited the dependency of TNBC on TGF-β for their growth, invasion and metastasis. They hypothesized that genes implied in bypassing replicative senescence caused by TGF-β could be “missing links” involved in converting TGF-β from tumor suppressor to tumor promoter (TGF-β paradox). Since amplification of Chr20q13 in cancer is often associated with immortalization and escape from cell senescence, they focused on a TGF-β inducible gene that is located at Chr20q13, TMEPAI (transmembrane prostate androgen induced). Strikingly, TMEPAI showed gene amplification in 47 of 97 breast cancers (48.5%), including 45/85 (53%) invasive ductal carcinomas and 2/11 (18%) invasive lobular carcinomas. The majority of tumors (72.3%) with TMEPAI copy number gain were of histologic grade 3 (34/47). Among 31 TNBCs, TMEPAI was amplified in 18 (58.1%) of them. The inventors' previous work suggests that amplified TMEPAI promotes TNBC growth and invasion, and that TMEPAI gene knockdown corrects the aggressive behavior of a prototypic TNBC (1).